Developmental Biology 哺乳动物性特征的发育机制 Female intemal Follicular genitalia OVARY Follicles (uterus, oviduct DXT Theca cervix, upper vagina) ANTe Genital Bipotential Mullerian duct SKY LAX sox2 Sertoli sFT AMH lIs b Regression IESTIS -+ Testosterone Genital tubercle urogenital sinus Penis prostate Wolffia Male internal duct genitalia didymus, vas deferens seminal vesicle) Figure 20.2 Postulated cascades leading to the for- chromosome)in conjunction with auto- major hormones. The first, anti mation of the sexual phenotypes in somal genes such as SOX9. The ovary Mullerian duct factor(AMH), causes mammals. The conversion of the genital makes thecal cells and granulosa cells, the Muillerian duct to regress. The sec the sri and WTi genes, since mice lack- ing estrogen. Under estrogen (first from tion of the Wolffian duct into the map ridge into the bipotential gonad needs which together are capable of synthesiz- ond, testosterone, causes the differenti ing either of these genes lack gonads. the mother, then from the gonads), the internal genitalia. In the urogenital The bipotential gonad appears to be Mullerian duct differentiates into the region, testosterone is converted into moved into the female pathway by the female genitalia and the offspring dihydrotestosterone(DHT), and this Wnt4 or DAXI genes and into the male develop the secondary sex characteris- hormone causes the morphogenesis of pathway by the SkY gene(on the Y tics of females. The testis makes two the penis and prostate
Developmental Biology 哺乳动物性特征的发育机制 LHX9
Developmental Biology 睾丸决定基因为Y染色体上的SRY (sex-determining region of the Y chromosome Fig 12.2 Sex reversal in humans due requent Rare to chromosomal exchange At meiosis exchange exchange in male germ cells, the X and Y chromo somes pair up(center panel) and there X XY×Y is often crossing over of the distal region (blue cross), which does not affect sexual development (left panel). On rare occasions SRY IN SRY crossing over involves a larger segment that includes the SRY gene(red cross so that the x chromosome now carnes this male-determining gene (right panel). After Goodfellow. P.N. et al. 1993 SRY是通过分析XX的men和XY的 women的DNA而发现的(1990) 它是一种编码223a的转录因子,含有 HMG DNA结合区
Developmental Biology 睾丸决定基因为Y染色体上的SRY (sex-determining region of the Y chromosome) SRY是通过分析XX的men和XY的women的DNA而发现的(1990)。 它是一种编码223 aa的转录因子，含有HMG DNA结合区
Developmental Biology Sry对睾丸发育的影响的实验证据 小鼠Sry基因也存在于Y染色体上,在未分化的生殖腺和 正在分化为睾丸的生殖腺中表达。转Sry基因的XX小鼠 可长出睾丸和雄性特征,但不能产生正常的精子。 XX - Control (A) (B) XY XX Figure 20.6 XX mouse transgenic for Sry is male. (A)Polymerase chain reaction followed by electrophoresis shows the presence of the Sry gene in normal XY males and in a transgenic XX Sry mouse. The gene is absent in the female XX littermate. (B)The as in an XY male(left).(From Koopman et al., 1991, photograph courtesy of the external genitalia of the transgenic mouse are male(right) and essentially the san authors
Developmental Biology 小鼠Sry基因也存在于Y染色体上，在未分化的生殖腺和 正在分化为睾丸的生殖腺中表达。转Sry基因的XX小鼠 可长出睾丸和雄性特征，但不能产生正常的精子。 Sry对睾丸发育的影响的实验证据 XY XX
Develop sryf的直接作用模型:s直接诱导雄性生殖嵴特异性基因的表达 Sry的间接作用模型:sn诱导生殖嵴细胞合成某种因子→中肾细胞进入生 殖嵴→诱导生殖嵴表皮细胞转变为睾丸支柱细胞、并表达雄性特异性基因。 Figure 17.7 12-1y Migration of the mewonephr cells into Sn gonadal rudn C)(mmtm钟 nd gonadal rudiments) were collected from 12-day embronic mice. One of the ice was market with a B-galactosidas tran xX+ Sry XOr XY oN XY .lrv or XX) I he goat and meone bine, usint gonadal tissue from unlabeled mice and meo nephros from Labeled mice. (A) Migration of mesonephric RTme cells into the gonad was seen when the gonadal cell wet GAy XY or when they were XX with an Sry transgene (N) No Mesons was Men when the gonad contained cither xX cela or xXY cells in whih the Y chromosome had a deletion in theSr gene. The sex chromosomes of the mesonephros did not nAkd上地 tthe"s ducts and the developing gonad in the l6 lay ation, (C) Intimate relation between the uy cytokeratin-s, wD). Wolfun duct(A, B after Cape eta 1999. photographs courtesy of B, Capel C from Sariola and urma 199), photograph courtesy of H Sariola. coculture A Sry: Allows migration -Sryt No mesonephric cell migration
Developmental Biology Sry的直接作用模型：Sry直接诱导雄性生殖嵴特异性基因的表达。 Sry的间接作用模型：Sry诱导生殖嵴细胞合成某种因子→中肾细胞进入生 殖嵴→诱导生殖嵴表皮细胞转变为睾丸支柱细胞、并表达雄性特异性基因
Developmental Biology 与睾丸命运决定有关的常染色体基因 Sox9:为含 HMG DNA结合区的转录因子。含一个额外的 SOX9的 SHuman将发育为mae;而75%的、只含一个有功能的 SOX9的 HUmans发育为 Ifemale或两性人 小鼠的Sox9只在雄性生殖嵴中表达,表达时间比Sry约晚 S0x9蛋白可与Amh的启动子结合,促进Amh的表达。 SF( steroidogenic factor1):为含 HMG DNA结合区的转录 因子。S们在雌雄小鼠的未分化的性腺中都表达,但分化开始后就局 限在XY小鼠的正在发育的睾丸中。SF1在睾丸支柱细胞中通过协助 Sox9而增强AM基因的表达( see next slide);而在睾丸的间质细胞中, 它可激活睾丸酮合成酶基因
Developmental Biology 与睾丸命运决定有关的常染色体基因 Sox9：为含HMG DNA结合区的转录因子。含一个额外的 SOX9的XX human 将发育为male; 而75%的、只含一个有功能的 SOX9的XY humans发育为female或两性人。 小鼠的Sox9只在雄性生殖嵴中表达，表达时间比Sry约晚。 Sox9蛋白可与Amh的启动子结合，促进Amh的表达。 SF1(steroidogenic factor 1)：为含HMG DNA结合区的转录 因子。Sf1在雌雄小鼠的未分化的性腺中都表达，但分化开始后就局 限在XY小鼠的正在发育的睾丸中。SF1在睾丸支柱细胞中通过协助 Sox9而增强AMH基因的表达(see next slide);而在睾丸的间质细胞中， 它可激活睾丸酮合成酶基因